Brain tumors, the most common solid tumors of childhood, represent a significant cause of neurological morbidity and mortality. For medulloblastoma and other primitive neuroectodermal tumors (PNET) of the CNS, the biology, treatment and delayed neurotoxicities are poorly understood despite its recognized importance as the most common childhood brain tumor. Moreover, the specialized problems posed by childhood brain tumors are only partially addressed by current brain tumor research centers and a more focused commitment is required. Our proposal identifies two overall objectives designed to explore the feasibility of developing a pediatric brain tumor research center at The Children's Hospital of Philadelphia (CHOP). The first objective is to develop an integrated, coordinated network of investigators who will examine laboratory and clinical issues specific to PNET and relevant to other childhood brain tumors. This objective will be accomplished by the Aims for the Program as a Whole, including specific mechanisms to: (1) improve communication and interaction between investigators; (2) attract promising young investigators and entice established researchers to address pediatric neuro-oncology topics; and (3) encourage trainees to pursue careers as clinician-scientists in pediatric neuro-oncology research. The second objective is to increase our understanding of the biology, treatment and delayed toxicities of therapy by conducting innovative research. This objective will be accomplished by the following exploratory projects which, together, represent a comprehensive approach to PNET: Project 1 will address the role of protein tyrosine kinase growth factors in PNET differentiation and pathogenesis; Project 2 will examine signal transduction pathways (phospholipase C) in PNET, Project 3 will evaluate innovative therapeutic approaches to PNET and other childhood brain tumors; Project 4 will use innovative methodologies to address the functional biology, prevention and treatment of treatment-associated brain injury in long-term survivors of PNET. The Neuro-Oncology Program at CHOP has received recognition for its clinical contributions. This proposal addresses the need for integrated program development that includes basic sciences and experimental therapeutics. It is further enhanced by recent events at The Children's Hospital of Philadelphia and University of Pennsylvania, including new Program leadership, faculty recruitments, and construction of research facilities. Together with our large brain tumor population, institutional commitments to the specialized problems of children, strong research environment from the surrounding University, and on-site access to NIH-funded specialized research centers relevant to this proposal, these strengths make CHOP an ideal site to explore the feasibility of developing a specialized center for pediatric brain tumor research.